A wound (i.e., a laceration or opening) in mammalian tissue results in tissue disruption and coagulation of the microvasculature at the wound face, and repair of such tissue represents an orderly, controlled cellular response to injury.
Tissue growth and repair are biologic systems where cellular proliferation and angiogenesis occur in the presence of an oxygen gradient. Wound healing represents an orderly, controlled cellular response to injury. The sequential morphologic and structural changes which occur during tissue repair have been characterized in great detail and have in some instances been quantified. Raftery, A. T., "Regeneration of Parietal and Visceral Peritoneum", Brit. J. Surg., Vol. 60, p. 293 (1973). All soft tissue wounds, regardless of size, heal in a similar manner. Injury results in tissue disruption and coagulation of the microvasculature at the edge of the wound. The cellular morphology consists of three distinct zones. The central avascular wound space is oxygen-deficient, acidotic, hypercarbic, and has high lactate levels. Adjacent to the wound space is a gradient zone of local anemia (ischemia) which is populated by dividing fibroblasts. Behind the leading zone is an area of active collagen synthesis characterized by mature fibroblasts and numerous newly-formed capillaries (i.e., neovascularization). While this new blood vessel growth (angiogenesis) is necessary for the healing of wound tissue, angiogenic agents have heretofore been unable to fulfill the long-felt need of providing the additional biosynthetic effects of tissue repair.
Despite the need for more rapid healing of wounds, i.e., severe burns, surgical incisions, lacerations and other trauma, there is presently no practical way to accelerate wound healing with pharmacological agents.
The invention comprises a method for increasing the rate of healing of wound tissue, comprising the application to such tissue of angiotensin II in an amount which is sufficient for said increase. As explained in the detailed description which follows, it has been found that the application of angiotensin II to wound tissue significantly increases the rate of wound healing, leading to a more rapid re-epithelialization and tissue repair.
The term angiotensin II refers to the octapeptide present in humans and other species, and has the sequence Asp-Arg-Val-Tyr-Ile-His-Pro-Phe. Angiotensin II is a known pressor agent and is commercially available.